We wish to determine whether the pattern we have seen for the release of adenosine after brief myocardial ischemia implies a role for this potent vasodilator in the metabolic autoregulation of coronary flow. In dogs and in pigs, we will examine the effects of drugs which are adenosine sparers or antagonists on segmental reactive hyperemic flow and on the concentration of adenosine in regional coronary venous blood. In man, we will study more completely the temporal relationship between adenosine release into the coronary sinus and the onset or subsidence of pacing-induced angina and lactate production. We are also determining whether the greater and yet reversible release of inosine and hypoxanthine following more prolonged ischemia is affected by increased MVO2 during the ischemic period and whether it can be used as a reliable index of the degree of ischemia. In pigs, these studies will include manipulation of rate, inotropy, and afterload in our preparation, which permits sampling of regional venous blood. In man, we will continue to explore the usefulness of these measurements as monitors of myocardial metabolism during ischemic cardiac arrest induced during surgery and during unstable angina.